The safety and efficacy of dabrafenib and trametinib in patients with glioma: A systematic review and meta-analysis.

BACKGROUND: Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents. METHODS: PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models. RESULTS: Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35-65%) for low-grade gliomas (LGG) and 40% (95% CI: 29-51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36-54%) for both glioma grades. The complete response rate was 13% (95% CI: 05-27%) for HGG and 5% (95% CI: 1-10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58-98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34-79%). Grade 1-4 adverse events occurred in 100% of LGG and 63% of HGG patients. CONCLUSIONS: Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.

Is add-on Bevacizumab therapy to Temozolomide and radiotherapy associated with clinical utility for newly diagnosed Glioblastoma? A systematic review and meta-analysis.

Bevacizumab, temozolomide (TMZ), and radiotherapy are three therapeutic methods, but the combination of them as a new approach for the treatment of newly diagnosed high-grade gliomas (HGGs) is still under investigation. Therefore, this study aims to evaluate the safety, efficacy, and clinical utility of this treatment approach for patients with glioblastoma (GBM). PubMed/Medline, Scopus, Embase, and Web of Science were systematically reviewed from inception to 24 August 2023. Relevant studies evaluating the therapeutic effect of adding Bevacizumab to TMZ-based chemotherapy and radiation therapy were enrolled. All statistical analysis was performed using the "meta" package of R. A total of 21 studies were included in this study. Our meta-analysis found that adding bevacizumab to standard therapy improved progression-free survival (PFS) in patients with newly diagnosed GBM. The pooled 6-month PFS rate was significantly higher with bevacizumab (79% vs. 56%, odds ratio 3.17). Overall survival (OS) showed modest improvements, with 2-year OS rates of 39% vs. 20% favoring bevacizumab. Radiological response rates varied, with a pooled overall response rate of 44% for bevacizumab-treated patients. The complete response rate was 16%, partial response 32%, and progressive disease 25%. Adverse events occurred in 62% of bevacizumab-treated patients. Common complications included fatigue, thrombocytopenia, and thromboembolic events. When added to standard therapy, bevacizumab demonstrates modest improvements in PFS and OS for newly diagnosedGBM. While it shows promise in short-term outcomes and radiological responses, long-term survival benefits remain limited. The risk of adverse events, particularly CNS hemorrhage, necessitates careful patient selection. These findings suggest that bevacizumab may have a role in treating high-grade gliomas, but its use should be individualized based on patient characteristics and risk-benefit assessment.

Anti-PD-1/PD-L1 inhibitor therapy for melanoma brain metastases: a systematic review and meta-analysis.

Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases. This systematic review and meta-analysis followed PRISMA guidelines. PICO criteria targeted melanoma brain metastasis patients treated with PD-1/PD-L1 inhibitors, assessing overall survival, progression-free survival, and complications. Inclusion criteria were English studies on humans using PD-1/PD-L1 inhibitors for melanoma brain metastases with > 10 patients. A total of 22 trials involving 1523 melanoma brain metastase patients treated with anti-PD-1/PD-L1 inhibitors were thoroughly analyzed. Our findings show the 6-month OS rate of 0.75 [95%CI:0.67-0.84], the 6-months PFS rate of 0.42 [95%CI:0.31-0.52], the 1-year OS rate of 0.63 [95%CI:0.52-0.74], the 1-year PFS rate was 0.45 [95%CI:0.32-0.58], the 18-months OS rate of 0.52 [95%CI:0.37-0.67], the 2-year OS rate of 50% [95% CI: (34%-65%)], the 2 year PFS rate of 0.36 (95%CI:0.23-0.50), the 3-year OS rate of 0.42 (95%CI:0.17-0.67), the 4-year PFS rate of 0.35 [95%CI:0.08-0.61], the 4-year OS rate of 0.29 [95%CI:0.01-0.56], the 5-year OS rate of 0.29 (95%CI:0.09-0.50), and the 5-year PFS rate of 0.11 (95%CI:0.03-0.19). The combined disease stability rate was 0.13 [95%CI:0.05-0.20], the progressive disease rate was 0.49 [95%CI:0.37-0.62], the partial response rate was 0.14 [95%CI:0.07-0.20], the object response rate was 0.35 [95%CI:0.24-0.46], and the complete response rate was 0.22 [95%CI:0.12-0.32]. In conclusion, our meta-analysis provides compelling evidence supporting the efficacy of PD-1/PD-L1 inhibitors in patients with melanoma brain tumors, as evidenced by favorable survival outcomes and disease control rates.

Safety and efficacy of flow redirection endoluminal device (FRED) for treatment of intracranial aneurysm; A systematic review and meta-analysis.

BACKGROUND: Previous research has shown promising results for treating intracranial aneurysms (IAs) with a flow redirection endoluminal device (FRED). In this systematic review and meta-analysis, we aimed to assess the safety and efficacy of this device by providing pooled estimates using the data from previous studies. METHODS: A systematic literature search of Web of Sciences, PubMed, Scopus, and Embase was performed until October 8th, 2023. After selecting the final articles, relevant data were extracted. Parameters relating to safety and efficacy were pooled using STATA software. Heterogeneity was assessed using I-squared and Cochran's Q. Funnel plots and Egger's regression methods were used to evaluate publication bias. Sensitivity analysis was also performed using the leave-one-out method. RESULTS: The data of 37 studies were used for meta-analysis. The rates of immediate adequate occlusion and complete occlusion were 0.51 (95% CI: 0.31-0.71) and 0.34 (95% CI: 0.16-0.53), respectively, while the rates of the adequate and complete occlusion at the latest follow-up were 0.90 (95% CI: 0.84-0.94) and 0.75 (95% CI: 0.65-0.84), respectively. The periprocedural complications rate was 0.04 (95% CI: 0.03-0.06), and the overall complications rate was 0.12 (95% CI: 0.09-0.15). The rate of good functional outcome was 0.99 (95% CI: 0.99-1.00) and the successful implantation rate was 1.00 (95% CI: 1.00-1.00). There was substantial heterogeneity among the reports for most of the evaluated parameters. CONCLUSION: FRED had high safety and efficacy in treating IAs, as evidenced by its high occlusion and low complication rates.

The clinical utility of autologous tumor lysate-loaded dendritic cell vaccination for patients with glioma: A systematic review and meta-analysis.

BACKGROUND: Dendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta-analysis examined DC vaccine efficacy and safety for gliomas. METHODS: This systematic review and meta-analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated. RESULTS: A total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6-month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%-100%]. Respectively, 12-month OS reported 75% [95%CI: 65%-85%] but declined to 32% [95%CI: 20%-43%] for 24-month OS. 6- and 12-month progression-free survival reached 49% [95%CI: 21%-77%] and 19% [95%CI:8%-30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%-42%], and 26% [95%CI: 10%-42%], though stable disease reached 33% [95%CI: 15%-51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%-57%]. CONCLUSIONS: In gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration.